Hexachloroethane → 6-Fluoro-3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine

HRID 2200017ノート

反応式

HRID 2200017 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:10]([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]2[CH3:18])=O)=[N:6][CH:7]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC.ClC(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1.C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:10]([N:12]3[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]3[CH3:18])=[N:9][N:8]=2)[CH:7]=1

参加物

7

反応物 4

HCID 6214HexachloroethaneHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 86687104(S)-2-Methyl-piperidine-1-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

生成物 1

HCID 866871056-Fluoro-3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine収率 82.8%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

To a stirred solution of Intermediate 2c (14.70 g, 58.27 mmol), Ph3P (30.56 g, 116.51 mmol) and Et3N (33 mL, 236.76 mmol) in THF (300 mL) at RT was added hexachloroethane (27.60 g, 116.58 mmol) during 10 min before then heating at 60° C. overnight. The cooled mixture was filtered and concentrated in vacuo to give a residual oil which was dissolved in DCM (200 mL) and extracted into dilute HCl (2M) until most product had been removed from the DCM phase by LCMS. These aqueous extracts were treated with solid NaOH (with cooling) to achieve ˜pH9 and extracted into DCM. Combined DCM extracts were washed with brine, dried (MgSO4), passed through a phase separation cartridge and concentrated in vacuo to give Intermediate 2d (11.30 g, 82%). LCMS (Method 3) Rt 2.99 min, m/z 235 [MH+]. 1H NMR (300 MHz, d6-d6-DMSO): 0.89 (3H, d, J 6.3), 1.40-1.88 (6H, m), 2.85-2.96 (1H, m), 3.18 (1H, dt, J 12.0, 4.5), 3.28-3.35 (1H, m), 7.42 (1H, ddd, J 10.0, 8.0, 2.3), 7.76 (1H, ddd, J 10.0, 4.9, 0.9), 8.31-8.35 (1H, m).

後処理

  1. filtrationThe cooled mixture was filtered
  2. concentrationconcentrated in vacuo
  3. customto give a residual oil which
  4. extractionextracted into dilute HCl (2M) until most product
  5. customhad been removed from the DCM phase by LCMS
  6. additionThese aqueous extracts were treated with solid NaOH (with cooling)
  7. extractionextracted into DCM
  8. washCombined DCM extracts were washed with brine
  9. dry with materialdried (MgSO4)
  10. custompassed through a phase separation cartridge
  11. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-16f5d80c42974be6b6b4eeb598117fb2
出典データセット
uspto-grants-2016_06
特許番号
US09359354B2

反応ノート

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